The subject of the invention is a process for the nucleophilic substitution on activated aromatics of the general formula XIV 
in which R1, R2, R3, R4 and R5 are the same or different and signify a hydrogen atom, a nitro group, a cyano group, an alkoxycarbonyl group with up to 5 C-atoms, an aldehyde group, an alkylearbonyl group with up to 5 C-atoms, an arylcarbonyl group or an amide group, whereby the radicals R1 to R5 cannot all simultaneously be a hydrogen atom and HAL stands for a halogen atom but especially for a fluorine atom, with nucleophils, such as alcohols, amines, sulphoximides, CH-acidic compounds of the formulae V to XI 
in dipolar aprotic solvents, especially dimethylformamide, with use of caesium. carbonate.
The process is preferred for the preparation of compounds of the general formula I 
in which HETN signifies an aromatic aza-heterocycle with, in all, 5 or 6 ring atoms, whereby up to 3 ring atoms can be nitrogen atoms, and up to two further aromatic carbon rings can be condensed on to the heterocycle and R1 to R5 have the above-mentioned meaning.
Compounds of the general formula I play an important part in medicinal chemistry. Thus, e.g. one finds the N-aryl-aza-heterocyclic structure in substances with anti-oestrogenic (E. Angerer, J. Strohmeier, J. Med. Chem. 30, 131, 1987), with analgesic (E. J. Glamkowski et al., J. Med. Chem. 28, 66, 1985), with anti-diabetic (R. B. Chapleo, G. P. Fagan, Ann. Drug 5 Data Rep. 15, 59, 1993), with anti-miciobial (A. G. Kamat, G. S. Gadaginamath, Indian J. Chem., Sect. B, 33, 255, 1994), with neuroleptic (J. Perregaard et al., J. Med. Chem. 35, 1092, 1.992), with anti-allergic (P. Ungast et al., J. Med. Chem. 32, 1360, 1989), with angiotensin-antagonistic (S. R. Stabler and Jahangir, Syn. Commun. 24, 123, 1994) and with PDGF receptor inhibitory action (Brian D. Palmer et al., J. Med. Chem. 41, 5457, 1998).
Compounds of the general formula I can be prepared according to various methods. A frequently used method consists in the reaction of aza-heterocycles with activated aryl halides in the presence of catalysts and/or bases or, in few cases, also without further additives, according to scheme 1: 
Thus, e.g. 1-(benzotriazol-1-yl)-2,4-dinitro-benzene can be obtained in 96% yield by 9 days boiling of benzotriazole in toluene (A. R. Katritzky, J. Wu, Synthesis 1994, 597).
4-Heterocyclicly-substituted nitrobenzenes and benzaldehydes can be obtained by reaction of the particular aza-heterocycles, such as e.g. benzotriazole, 1,2,4-triazole or benzimidazole, with 4-fluorobenzaldehyde or 4-fluoro- or 4-chlorobenzaldehyde in DMSO or DMF at 100xc2x0 C. (D. J. Gale, J. F. K. Wilshire, Aust. J. Chem. 23, 1063, 1970; J. Rosevear, J. F. K. Wilshire, Aust. J. Chem. 44, 1097, 1991).
Nitrophenylazoles can be prepared by Ullmann condensation of azoles with aryl halides in pyridine in the presence of potassium carbonate and copper (II) oxide at high temperatures and long reaction times (M. A. Khan, J. B. Polys, J. Chem. Soc. (C), 1970, 85; A. K. Khan, E. K. Rocha, Chem. Pharm. Bull. 25, 3110, 1977) or, however, by reaction of azoles with suitable fluoronitrobenzenes in DMSO at comparatively high temperature and in the presence of potassium carbonate (M. F. Mackay, G. J. Trantino, J. F. Wilshire, Aust. J. Chem. 46, 417, 1993).
1-Arylindoles with activating substituents in the aryl part were obtained by reaction of indole with activated aryl halides in the presence of 37% KF/Al2O3 and catalytic amounts of crown ethers in DMSO at 120xc2x0 C. (W. J. Smith, J. Scott Sawyer, Tetrahedron Lett. 37, 299, 1996).
There is also described the arylation of azoles with activated aryl halides in the presence of bases, such as caesium carbonate and sodium tert.-butylate, whereby, however, the presence of palladium catalysts is additionally necessary and the reaction itself requires high temperatures (65xc2x0 to 120xc2x0 C.) and long reaction times (3 to 48 hours) (G. Mann, J. F. Hartwig, M. D. Driver, C. Fernandez-Rivas, J. Am. Chem. Soc. 120, 827, 1998; I. P. Beletskaya, D. V. Davydov, M. MorenoManas, Tetrahedron Lett. 39, 5617, 1998).
The use of caesium carbonate as reagent in the case of carbon-heteroatom coupling reactions is also known but further special catalysts must additionally always be used in such reactions (Christopher G. Frost, Paul Mendonca, J. Chem. Soc., Perkin Trans. 1, 1998, 2615).
In general, from the above-given examples, it can be deduced that for arylations of azoles with activated aryl halides, relatively drastic conditions, such as high temperatures, long reaction times, as well as special catalysts, are frequently necessary.
In connection with the synthesis of a potentially anti-cancer compound, the reaction was investigated by use of morpholinopropanol (III) with o-nitrofluorobenzene (II) (scheme 2): 
Based on our experience with the system caesium carbonate/dimethylformamide for the preparation of carbonates from alcohols and alkyl/aryl halides (DE 199 05 222.0) and of heterocyclic carbamates from aza-heterocycles and alkyl/aryl halides, we investigated whether this system is also suitable for the above reaction.
Surprisingly, it was found that this reaction leads at 23xc2x0 C. within 48 hours to the desired product (IV) in 82% yield.
On the basis of this finding, it was now investigated whether other nucleophils, such as e.g. the nucleophils V to X also react with 2-fluoronitrobenzene at room temperature in the system caesium carbonate/dimethylformamide: 
It was found that these reactions also give the desired products in good to very good yield at room temperature within 24 to 64 hours. The reaction of 2,5-difluoronitrobenzene (XII) with malonic acid dimethyl ester (XI) at room temperature in the system caesium carbonate/dimethylformamide also leads after 24 hours in 98% yield to the desired product XIII (scheme 3): 
The preparation of compound XIII is described in the literature with use of sodium hydride in dimethyl sulphoxide at 100xc2x0 C. in 96% yield (Li Sun et al., J. Med. Chem. 41, 2588, 1998).
Encouraged by these results, the arylation of aza-heterocycles with activated aromatics of the general formula XIV 
in which R1 to R5 have the above-given meaning and HAL stands for a halogen atom but especially for a fluorine atom, was investigated in the system caesium carbonate/dimethylformamide.
Surprisingly, it was found that almost all azaheterocycles used already react at room temperature in the presence of caesium carbonate/dimethylformamide with activated fluoroaromatics of the general formula XV to give compounds of the general formula I 
Instead of dimethylformamide, there can also be used other dipolar aprotic solvents, such as e.g. dimethylacetamide, acetonitrile, dimethylsulphoxide, acetone or N-methylpyrrolidone; however, the reaction times at room temperature are then distinctly longer and the yields often lower.
The process procedure in the case of the preparative carrying out of the arylation is very simple. One dissolves equimolar amounts of azaheterocycle and activated aromatics of the general formula XIV but especially of the general formula XV at room temperature in a suitable dipolar aprotic solvent, especially dimethylformamide, adds thereto a 2 to 4 molar excess of anhydrous caesium carbonate and stirs at room temperature until the reaction is ended. The reaction is monitored by means of thin layer chromatography. In the case of less reactive aromatics, in a few cases the reaction temperature must be increased to about 80xc2x0 C.
At the end of the reaction, one pours the suspension on to water, extracts the product with ethyl acetate and purifies the product obtained after ev;xcx9cporation of the organic phase with the methods usual in organic chemistry, e.g. by crystallisation or chromatography.
The invention is illustrated and explained by the following embodimental examples: